Aminopterin, or N-4-[[2,4-diamino-6-pteridinyl)-methyl]amino]benzoy-1]-L-glutamic acid, is a potent antifolate useful for treating a variety of human diseases. Rees et al. noted in 1964 that aminopterin instability was a problem in the tablet previously produced and marketed by Lederle Laboratories [Rees et al., Arch. Dermatol. 90:544-52, 1964]. Cole noted that liquid dosage forms degraded to folic acid over time [Cole et al., Clin. Cancer Res. 11(21):2005].
The therapeutic index of aminopterin is very narrow, and therefore accurate dosing is essential to achieve optimum efficacy and avoid harmful side-effects and potential lethality. Unstable dosage forms lead to inaccurate dosing, and risk to the patient.